First Online: 01 March 2011Received: 03 August 2010Revised: 10 February 2011Accepted: 01 March 2011

Abstract

IntroductionSepsis has been identified as a risk factor for human cytomegalovirus CMV reactivation in critically ill patients. However, the contribution of CMV reactivation on morbidity and mortality is still controversial. Therefore, we analyzed the incidence and impact of CMV reactivation on outcome in patients with severe sepsis.

MethodsIn a prospective longitudinal double-blinded observational study, 97 adult nonimmunosuppressed CMV-seropositive patients with new onset of severe sepsis were included. Leukocytes, plasma and tracheal secretions were examined weekly for CMV-DNA by PCR. Tracheal secretions were additionally tested for HSV Herpes Simplex Virus-DNA. The influence of CMV-reactivation on the endpoints was analysed by Cox proportional-hazard regression analysis. Time-dependency was evaluated by landmark analysis.

ResultsSix out 97 died and five were discharged from the hospital within 72 hours and were excluded of the analysis. CMV reactivation occurred in 35 of the 86 40.69% analysed patients. HSV infection occurred in 23 of the 35 65.7% CMV reactivators. In 10 patients CMV-plasma-DNAemia appeared with a DNA-content below 600 copies-ml in four cases and a peak amount of 2,830 copies-ml on average. In patients with and without CMV reactivation mortality rates were similar 37.1% vs. 35.3%, P = 0.861, respectively. However, in the multivariate COX regression analyses CMV reactivation was independently associated with increased length of stay in the ICU 30.0, interquartile range 14 to 48 vs. 12.0, interquartile range 7 to 19 days; HR hazard ratio 3.365; 95% CI confidence interval 1.233 to 9.183, P = 0.018 and in the hospital 33.0, interquartile range 24 to 62 vs. 16.0, interquartile range 10 to 24 days, HR 3.3, 95% CI 1.78 to 6.25, P < 0.001 as well as prolonged mechanical ventilation 22.0, interquartile range 6 to 36 vs. 7.5, interquartile range 5 to 15.5 days; HR 2.6,CI 95% 1.39 to 4.94; P < 0.001 and impaired pulmonary gas exchange six days, interquartile range 1 to 17, vs. three, interquartile range 1 to 7, days in reactivators vs. non-reactivators, P = 0.038. HSV reactivation proved not to be a risk factor for these adverse effects.

ConclusionsThese data indicate an independent correlation between CMV reactivation and increased morbidity in the well-defined group of nonimmunosuppressed patients with severe sepsis, but CMV reactivation had no impact on mortality in this group with low CMV-DNA plasma levels. Thus, the potential harms and benefits of antiviral treatment have to be weighed cautiously in patients with severe sepsis or septic shock.

AbbreviationsACCPAmerican College of Chest Physicians

CIconfidence interval

CMVcytomegalovirus

HRhazard ratio

HSVherpes simplex virus

LOSlength of stay

SAPSSimplified Acute Physiology Score

SCCMSociety of Critical Care Medicine

SOFASimplified Organ Failure Assessment.

Electronic supplementary materialThe online version of this article doi:10.1186-cc10069 contains supplementary material, which is available to authorized users.